tbuckley/cabot-search huggingface dataset:
Perspectives of Latinx Individuals Who Were Unvaccinated and Hospitalized for COVID-19
Authors: Lilia Cervantes, Cynthia A. Hazel, Diana Mancini, Rocio I. Pereira, Laura J. Podewils, Sarah A. Stella, Joshua Durfee, Alana Barshney, John F. Steiner
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Latinx individuals in the United States have lower COVID-19 vaccination rates and higher rates of COVID-19 infections, hospitalizations, and deaths than non-Latinx White individuals. Little is known about the perspectives of Latinx adults who had not received the COVID-19 vaccination and were hospitalized for COVID-19. <h3>Objective</h3> To describe the perspectives of Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19. <h3>Design, Setting, and Participants</h3> This qualitative study was conducted using semistructured phone interviews with 25 Latinx adults who were unvaccinated and survived a COVID-19 hospitalization in a public safety net hospital in Colorado from February to November 2021. Interviews were audio recorded, and transcripts were analyzed using thematic analysis. <h3>Main Outcomes and Measures</h3> Themes and subthemes of perspectives on vaccination. <h3>Results</h3> Among 25 adults (14 [56.0%] women, 11 [44.0%] men; mean [SD] age, 51 [15] years) who participated, all participants self-identified as Latino, Latina, or Latinx or Hispanic. There were 11 individuals who relied on emergency Medicaid (hospital coverage for Denver residents who are undocumented), while 10 individuals (40.0%) were essential workers and 13 individuals (52.0%) were unemployed. In interviews, 3 themes (with subthemes) were identified: factors associated with vaccination after hospitalization (subthemes: fear of death, avoiding hospitalization and reinfection, convinced COVID-19 is real, and responded to pressure from others), concerns about the COVID-19 vaccine (subthemes: experimental status and short timeline for production, contents of vaccine unknown or concerning, vaccine considered ineffective, worrisome immediate and long-term adverse effects, mixed and conflicting information, and government aimed to control or mark population through vaccination), and opportunities to improve vaccine uptake (subthemes; sharing personal experiences through social media, testimonials about minimal vaccine adverse effects, connecting with friends and family about the hospitalization experience, making the vaccine more accessible, and connecting with trusted sources of information). <h3>Conclusions and Relevance</h3> This study found that Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19 were motivated to engage in advocacy to encourage vaccination in their communities. These findings suggest that supporting patient advocacy after hospital discharge and continued efforts to create low-barrier, patient-informed public health strategies may be associated with increased vaccine uptake in Latinx communities.
Changes in Youth Cannabis Use After an Increase in Cannabis Minimum Legal Age in Quebec, Canada
Authors: Hai V. Nguyen, Shweta Mital
Journal: JAMA Network Open (2022)

<h3>Importance</h3> In January 2020, Quebec raised the minimum legal age (MLA) for cannabis from 18 to 21 years. Evidence is needed to inform the ongoing debate on this policy. Although proponents believe that a higher MLA will protect youths from the harms of cannabis use, critics argue that it will push them back to the illegal market. <h3>Objective</h3> To investigate changes in youth cannabis use after an increase in MLA for cannabis in Quebec. <h3>Design, Setting, and Participants</h3> This cross-sectional study with difference-in-differences analysis compared changes in cannabis use among youths aged 15 to 20 years in Quebec vs all other Canadian provinces before and after Quebec’s increase in MLA. All estimates in descriptive and regression analyses were weighted. Nationally representative data from the National Cannabis Surveys 2018-2020 were used. <h3>Intervention</h3> Increase in MLA for cannabis in Quebec implemented in January 2020. <h3>Main Outcomes and Measures</h3> Past-3-month cannabis use. <h3>Results</h3> The study sample included 1005 respondents (mean [SD] age, 17.5 [1.7] years; 50.2% [SD, 50.0%] male). After policy implementation, the increase in past-3-month cannabis use among youths aged 18 to 20 was 16.4 percentage points (95% CI, −27.3 to −5.5 percentage points;<i>P</i> = .01), or 51%, lower in Quebec than in other provinces. Meanwhile, no significant change in cannabis use among youths aged 15 to 17 years was found. The results were robust to several checks, including accounting for possible confounding effects of the COVID-19 pandemic on cannabis use. <h3>Conclusions and Relevance</h3> In this study, an increase in the MLA from 18 to 21 years in Quebec was associated with a significantly lower increase in cannabis use among youths aged 18 to 20 years but no change in cannabis use among those aged 15 to 17 years. These findings can help to alleviate concerns that youths would switch to illegal markets in response to a higher MLA.
50P Direct-acting oral anticoagulants prescribing pattern in patients with gynaecological cancer: Results of a survey among Italian oncologists belonging to MITO group and AIOM society
Authors: V. Tuninetti, A. Milani, S. Pignata, D. Lorusso, D. Castaldo, U.F.F. De Giorgi, A. Savarese, N. Biglia, G. Scandurra, S. Testa, G. Mangili, M. Di Maio, M. Turinetto, S. Mammoliti, G. Scotto, G. Artioli, G. Valabrega
Journal: Annals of Oncology (2022)
Neoadjuvant Chemotherapy Plus Immunotherapy in Early-Stage Resectable Non–Small-Cell Lung Cancer
Authors: Antonio Passaro, Ilaria Attili, Filippo de Marinis
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology , to patients seen in their own clinical practice.
The pancreatic β-cell in ageing: Implications in age-related diabetes
Authors: Eva Tudurí, Sergi Soriano, Lucía Almagro, Eduard Montanya, Paloma Alonso-Magdalena, Ángel Nadal, Ivan Quesada
Journal: Ageing Research Reviews (2022)

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt β-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic β-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of β-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as β-cell proliferation, apoptosis and cell identity that can influence β-cell mass. Age-related changes also affect β-cell function at distinct steps including electrical activity, Ca2+ signaling and insulin secretion, among others. We will consider the potential impact of these alterations and those mediated by senescence pathways on β-cells and their implications in age-related T2D. Finally, given the great diversity of results in the field of β-cell ageing, we will discuss the sources of this heterogeneity. A better understanding of β-cell biology during ageing, particularly at older ages, will improve our insight into the contribution of β-cells to age-associated T2D and may boost new therapeutic strategies.
Retracted: Posttranslational regulation of polycystin‐2 protein expression as a novel mechanism of cholangiocyte reaction and repair from biliary damage
Journal: Hepatology (2022)

Retraction: Spirli, C., Villani, A., Mariotti, V., Fabris, L., Fiorotto, R. and Strazzabosco, M. (2015), Posttranslational regulation of polycystin-2 protein expression as a novel mechanism of cholangiocyte reaction and repair from biliary damage. Hepatology, 62: 1828-1839. https://doi.org/10.1002/hep.28138. The above article, published online on 27 August 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the corresponding author, the journal's Editor in Chief Dr. Gregory Gores, and Wiley Periodicals LLC. The retraction has been agreed upon due to recently verified concerns regarding data authenticity rendering the conclusions uncertain. Several figures included in the article were found to have been falsified.
2P Spectrum of BRCA1, BRCA1, ATM and PALB2 alleles in ovarian cancer patients from North Caucasus
Authors: E. Imyanitov, E. Bakayeva, A. Romanko, I. Stepanov, L. Sultanova, Z. Khamgokov, M. Bolieva, A. Epkhiev, M. Chakhkieva, I. Khabriev, M. Murachuev, A. Sokolenko
Journal: Annals of Oncology (2022)
Proteogenomic characterization of cholangiocarcinoma
Authors: Mengjie Deng, Peng Ran, Lingli Chen, Yunzhi Wang, Zixiang Yu, Ke Cai, Jinwen Feng, Zhaoyu Qin, Yanan Yin, Subei Tan, Yang Liu, Chen Xu, Guoming Shi, Yuan Ji, Jian‐Yuan Zhao, Jian Zhou, Jia Fan, Yingyong Hou, Chen Ding
Journal: Hepatology (2022)

Background and Aims: Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform biological processes and treatment vulnerabilities. Approach and Results: Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA. Proteomic clustering identified three subtypes with distinct clinical outcomes, molecular features, and potential therapeutics. Phosphoproteomics characterized targetable kinases in CCA, suggesting strategies for effective treatment with CDK and MAPK inhibitors. Patients with CCA with HBV infection showed increased antigen processing and presentation (APC) and T cell infiltration, conferring a favorable prognosis compared with those without HBV infection. The characterization of extrahepatic CCA recommended the feasible application of vascular endothelial‐derived growth factor inhibitors. Multiomics profiling presented distinctive molecular characteristics of the large bile duct and the small bile duct of intrahepatic CCA. The immune landscape further revealed diverse tumor immune microenvironments, suggesting immune subtypes C1 and C5 might benefit from immune checkpoint therapy. TCN1 was identified as a potential CCA prognostic biomarker, promoting cell growth by enhancing vitamin B12 metabolism. Conclusions: We characterized the proteogenomic landscape of 217 CCAs with 197 paired normal adjacent tissues and identified their subtypes and potential therapeutic targets. The multiomics analyses with other databases and some functional validations have indicated strategies regarding the clinical, biological, and therapeutic approaches to the management of CCA.
Unraveling protein dynamics to understand the brain – the next molecular frontier
Authors: Kyle D. Brewer, Sophia M. Shi, Tony Wyss-Coray
Journal: Molecular Neurodegeneration (2022)

Abstract The technological revolution to measure global gene expression at the single-cell level is currently transforming our knowledge of the brain and neurological diseases, leading from a basic understanding of genetic regulators and risk factors to one of more complex gene interactions and biological pathways. Looking ahead, our next challenge will be the reliable measurement and understanding of proteins. We describe in this review how to apply new, powerful methods of protein labeling, tracking, and detection. Recent developments of these methods now enable researchers to uncover protein mechanisms in vivo that may previously have only been hypothesized. These methods are also useful for discovering new biology because how proteins regulate systemic interactions is not well understood in most cases, such as how they travel through the bloodstream to distal targets or cross the blood–brain barrier. Genetic sequencing of DNA and RNA have enabled many great discoveries in the past 20 years, and now, the protein methods described here are creating a more complete picture of how cells to whole organisms function. It is likely that these developments will generate another transformation in biomedical research and our understanding of the brain and will ultimately allow for patient-specific medicine on a protein level.
LILRB2-mediated TREM2 signaling inhibition suppresses microglia functions
Authors: Peng Zhao, Yuanzhong Xu, Lu-Lin Jiang, Xuejun Fan, Zhiqiang Ku, Leike Li, Xiaoye Liu, Mi Deng, Hisashi Arase, Jay-Jiguang Zhu, Timothy Y. Huang, Yingjun Zhao, Chengcheng Zhang, Huaxi Xu, Qingchun Tong, Ningyan Zhang, Zhiqiang An
Journal: Molecular Neurodegeneration (2022)

Abstract Background Microglia plays crucial roles in Alzheimer’s disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs. Methods To specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)–derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory cytokines. Effects of the LILRB2 antagonist antibody on microglial responses to amyloid plaques were further studied in vivo using stereotaxic grafted microglia in 5XFAD mice. Results We confirmed the expression of both LILRB2 and TREM2 in human brain microglia using immunofluorescence. Upon co-ligation of the LILRB2 and TREM2 by shared ligands oAβ or PS, TREM2 signaling was significantly inhibited. We identified a monoclonal antibody (Ab29) that blocks LILRB2/ligand interactions and prevents TREM2 signaling inhibition mediated by LILRB2. Further, Ab29 enhanced microglia phagocytosis, TREM2 signaling, migration, and cytokine responses to the oAβ-lipoprotein complex in hMGL and microglia cell line HMC3. In vivo studies showed significantly enhanced clustering of microglia around plaques with a prominent increase in microglial amyloid plaque phagocytosis when 5XFAD mice were treated with Ab29. Conclusions This study revealed for the first time the molecular mechanisms of LILRB2-mediated inhibition of TREM2 signaling in microglia and demonstrated a novel approach of enhancing TREM2-mediated microglia functions by blocking LILRB2-ligand interactions. Translationally, a LILRB2 antagonist antibody completely rescued the inhibition of TREM2 signaling by LILRB2, suggesting a novel therapeutic strategy for improving microglial functions.
36P Factors associated with platinum resistance in ovarian cancer patients receiving neoadjuvant chemotherapy
Authors: Q. Gao, L. Xingyu, H. Ting, X. Jiao, Z. Yingjun, G. Ma, Y. Huo, L. Ming, Z. Peng, J. Chi, S. Zeng, Y. Yuyy
Journal: Annals of Oncology (2022)
Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS
Authors: Jinping Wang, Chang Qu, Xinyue Shao, Guoqiang Song, Jingyu Sun, Donghong Shi, Ran Jia, Hailong An, Hongjun Wang
Journal: Bioactive Materials (2022)

Human cancers typically express a high level of tumor-promoting mutant p53 protein (Mutp53) with a minimal level of tumor-suppressing wild-type p53 protein (WTp53). In this regard, inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy. Herein, a new carrier-free nanoprodrug (i.e., Mn-ZnO2 nanoparticles) was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species (ROS) within tumor to regulate the p53 protein for high anti-tumor efficacy. In response to the mild tumor acidic environment, the released Zn2+ and H2O2 from Mn-ZnO2 NPs induced ubiquitination-mediated proteasomal degradation of Mutp53, while the liberative Mn2+ and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level. Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical (•OH) through the Fenton-like reaction. With the integration of multiple functions (i.e., carrier-free ion and ROS delivery, tumor accumulation, p53 protein modulation, toxic •OH generation, and pH-activated MRI contrast) in a single nanosystem, Mn-ZnO2 NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.
Clinical characteristics, prognostic indicators, and survival outcomes in intravascular lymphoma: Mayo Clinic experience (2003–2018)
Authors: Karan Seegobin, Zhuo Li, Muhamad Alhaj Moustafa, Umair Majeed, Jing Wang, Liuyan Jiang, Justin Kuhlman, David Menke, Ke Li, Mohamed A. Kharfan‐Dabaja, Ernesto Ayala, Madiha Iqbal, Grzegorz S. Nowakowski, Thomas M. Habermann, Thomas E. Witzig, Patrick Johnston, Carrie Thompson, Stephen Ansell, Han W. Tun
Journal: American Journal of Hematology (2022)

Intravascular lymphoma (IVL) is a rare extranodal non-Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003-2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS-IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non-CNS-IVL patients with abnormal FDG-PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS-IVL and 63.5% (35/55) had non-CNS-IVL. CNS-IVL group consists of clinically isolated CNS involvement (CNS-only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M-IVL) (14.5%; 8/55). Non-CNS-IVL group consists of clinically isolated skin involvement (skin-only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P-IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B-cell IVL. Rituximab + high-dose methotrexate-based regimen were used in 75% (12/16) of CNS-IVL patients and RCHOP in 60% (17/28) of non-CNS-IVL patients. Estimated 5-year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin-only IVL was associated with excellent survival. Platelet count <150x109 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.
Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer
Authors: Isabel Heidegger, Georgios Fotakis, Anne Offermann, Jermaine Goveia, Sophia Daum, Stefan Salcher, Asma Noureen, Hetty Timmer-Bosscha, Georg Schäfer, Annemiek Walenkamp, Sven Perner, Aleksandar Beatovic, Matthieu Moisse, Christina Plattner, Anne Krogsdam, Johannes Haybaeck, Sieghart Sopper, Stefanie Thaler, Markus A. Keller, Helmut Klocker, Zlatko Trajanoski, Dominik Wolf, Andreas Pircher
Journal: Molecular Cancer (2022)

Abstract Background Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME. Methods TEC isolated from 67 fresh radical prostatectomy (RP) specimens underwent multi-omic ex vivo characterization as well as orthogonal validation of both TEC functions and key markers by immunohistochemistry (IHC) and immunofluorescence (IF). To identify cell–cell interaction targets in TEC, we performed single-cell RNA sequencing (scRNA-seq) in four PCa patients who underwent a RP to catalogue cellular TME composition. Targets were cross-validated using IHC, publicly available datasets, cell culture expriments as well as a PCa xenograft mouse model. Results Compared to adjacent normal endothelial cells (NEC) bulk RNA-seq analysis revealed upregulation of genes associated with tumor vasculature, collagen modification and extracellular matrix remodeling in TEC. PTGIR, PLAC9, CXCL12 and VDR were identified as TEC markers and confirmed by IF and IHC in an independent patient cohort. By scRNA-seq we identified 27 cell (sub)types, including endothelial cells (EC) with arterial, venous and immature signatures, as well as angiogenic tip EC. A focused molecular analysis revealed that arterial TEC displayed highest CXCL12 mRNA expression levels when compared to all other TME cell (sub)populations and showed a negative prognostic role. Receptor-ligand interaction analysis predicted interactions between arterial TEC derived CXCL12 and its cognate receptor CXCR4 on angiogenic tip EC. CXCL12 was in vitro and in vivo validated as actionable TEC target by highlighting the vessel number- and density- reducing activity of the CXCR4-inhibitor AMD3100 in murine PCa as well as by inhibition of TEC proliferation and migration in vitro. Conclusions Overall, our comprehensive analysis identified novel PCa TEC targets and highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis in PCa. Graphical Abstract
20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC)
Authors: D. Lorusso, N. Colombo, A. Casado Herraez, A.D. Santin, E. Colomba, D.S. Miller, K. Fujiwara, S. Pignata, S.E. Baron-Hay, I.L. Ray-Coquard, R. Shapira-Frommer, Y.M. Kim, M. McCormack, R. Massaad, A. Martin Nguyen, Q. Zhao, J. McKenzie, V.S. Prabhu, V. Makker
Journal: Annals of Oncology (2022)
12P Any size of lymph node metastasis should be considered N1 in patients with cervical cancer
Authors: D. Cibula, K. Benešová, J. Klát, H. Falconer, S. Kim, L. Van Lonkhuijzen, A. Lopez, D. Isla, F. Landoni, J. Kostun, R. Dos Reis, D. Odetto, I. Zapardiel, M. Borčinová, J. Jarkovský, V. Javůrková, S. Salehi, N. Abu-Rustum, L. Dostálek
Journal: Annals of Oncology (2022)
4P Targeting PI3K/AKT/mTOR pathway in platinum-resistant ovarian high-grade serous carcinoma: Translational analysis from the randomized phase II OCTOPUS trial
Authors: G. Giannone, D. Ennis, H.B. Mirza, Z. Cheng, J. McDermott, L-A. Lewsley, A.R. Clamp, R.A. Herbertson, R.M. Glasspool, J. Krell, S. Hinsley, U. Banerji, R. Riisnaes, S. Banerjee, I. McNeish
Journal: Annals of Oncology (2022)
Morphologic characteristics of cutaneous immune-related adverse events in patients receiving immune checkpoint inhibitors combined with other anticancer therapies: A multicenter retrospective study
Authors: Maria S. Asdourian, Ted V. Jacoby, Nishi Shah, Leah L. Thompson, Tracey Otto, Yevgeniy R. Semenov, Nicole R. LeBoeuf, Kerry L. Reynolds, Anna K. Dewan, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2022)
26P Uterine sarcoma: A retrospective Tunisian study of 103 cases
Authors: E. Ouertani, Y. Yahyaoui, Z. Ghodhbani, F. Letaief-Ksontini, A. Gabsi, K. Meddeb, M. Ayadi, A. Mokrani, N. Chraiet, H. Rais, Y. Zenzri, H. Ben Mansour, A. Mezlini
Journal: Annals of Oncology (2022)